The First Asymmetric Total Syntheses and Determination of Absolute Configurations of Xestodecalactones B and C

Abstract

The first efficient asymmetric total syntheses of xestodecalactones B and C have been accomplished in 10 steps with an overall yield of 22 and 20.2%, respectively. The key steps involve the utility of Evans oxazolidinone-mediated syn-aldol condensations to establish the C-9 configuration and the macrolide ring formation by intramolecular acylation. The absolute configurations of xestodecalactones B and C have been determined via these syntheses.

An efficient stereoselective total synthesis of 11β-methoxycurvularin

“…After stirring for 20 min, MeI (448 mg, 3.15 mmol) was added slowly and the resulting mixture was stirred for a further 2 h. After completion, the reaction was quenched with ice-cold H 2 O (10 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried over anhydrous Na 2 SO 4 , the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (EtOAc/hexanes, 1:9) to afford compound 9 as a yellow oily liquid (275 mg, 85% (8). n-BuLi (1.6 M in hexanes, 1.22 mL, 1.83 mmol) was added dropwise to a solution of 9 (250 mg, 1.22 mmol) in anhydrous THF (20 mL) at -78 °C under N 2 atmosphere.…”

“…Accordingly, the aromatic portion was expected to arise from the readily available 3,5-dimethoxyphenylacetic acid 7. 7,8 Retrosynthesis of the 12-membered lactone ring 5 led to a known compound 6 along with the key fragment 8, which in turn could be prepared from 9 and 10 in 65% yield. The fragment 9 was synthesized from homopropargyl alcohol 12 in seven steps.…”

Application of aluminum triiodide in organic synthesis

“…The AlI 3 -TBAI combination has also been applied in syntheses of other natural products including isocladosorpin (111a), 80 sporostain (111b), 81 11-α-methoxycurvularin (111c) and 11-β-methoxycurvularin (111d) 82,83 as well as xestodecalactone A (113), 84 B and C (115), 85 see Scheme 9 and Scheme 10. A deoxydehydration product (116) was obtained from 112 at ambient temperature in 94% yield during the synthesis of xestodecalactone C. 86 The naturally occurring sporostain (111b) is an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase (cAMP-PDE).…”

Recent progress regarding the bioactivities, biosynthesis and synthesis of naturally occurring resorcinolic macrolides

“…Another asymmetric total synthesis of 58 was later accomplished utilizing a Diels-Alder strategy by Danishefsky's group [106] . The first efficient asymmetric total syntheses of xestodecalactones B (59) and C (60) were accomplished by Liang et al (Scheme 12) [107] . These compounds were synthesized in 10 steps with overall yields of 22% and 20.2%, respectively.…”